1. Field of the Invention
The present invention relates to improved needle designs for live vaccines and, in particular, live vaccines for Marek""s and other diseases affecting chicken and other avian species, as well as for live microorganisms in general. More specifically, the present invention relates to a pair of needle assemblies having a needle and needle retainer which minimizes turbulence and damage to the live cells during transfer of vaccine fluids into and out of a standard syringe.
2. Prior Art
Marek""s disease is a viral disease of chickens resulting in a type of cancer, and is one of the most serious threats to poultry health. This virus lies latent in T-cells, which are a type of white blood cells. T-cells are an integral part of the immune system response which is the bird""s natural defense against disease. Within three weeks of infection, the fatal virus manifests as aggressive tumors in the spleen, liver, kidney, gonads, skin and muscle of the infected bird.
Marek""s disease is a herpesvirus-induced lymphoprolifertive disease that occurs naturally in chickens. Since the advent of the turkey herpesvirus vaccine (HVT), newly hatched chicks have been routinely inoculated against the disease prior to being placed in the brooder houses. Although HVT vaccine is generally quite effective, occasionally inoculated flocks experience heavy Marek""s disease losses. More recently, it has been found that by proper selection of both the site and time of inoculation, embryonic vaccination can be effective in the control of poultry diseases. It is essential that the egg be injected during the final quarter of the incubation period, and that the inoculate be injected within either of the regions defined by the amnion or the yolk sac. Under these conditions, the embryo will favorably respond immunologically to the vaccine with no significant impairment of its prenatal development.
A live cell-associated virus vaccine of tissue culture origin typically contains the Rispens strain, the SB1 strain of the chicken herpes-virus and the FC 126 HVT strain of the turkey herpes virus alone or in combination. The vaccine is presented in glass ampules containing concentrated vaccine, typically 1000 doses each, with a specified titer defined as Plaque Forming Units (xe2x80x9cPFUsxe2x80x9d). The vaccine product is stored in a frozen condition typically in liquid nitrogen freezer and shipped in liquid nitrogen. A special sterile diluent is supplied in a separate package, typically a sealed plastic bag with appropriate injection port and delivery tube opening. The vaccine is reconstituted by thawing the frozen vaccine in the glass ampule. The ampule is then broken open and the liquid vaccine product is withdrawn from the ampule using a standard needle and syringe. The diluent is stored at room temperature until use when the concentrated vaccine product withdrawn from the ampule by the needle and syringe is then injected into the diluent contained in the sealed plastic bag through the bag injection port. The reconstituted vaccine is then ready for delivery from the sealed bag through the delivery tube.
There are various factors that affect the level of PFUs delivered by a live cell associated vaccine, such as Marek""s vaccine, to an inoculated specimen. Most of these factors occur during the vaccine reconstitution and in the delivery process and both have to do with vaccine handling, temperature, turbulence in the syringe, air pressure, friction, pH, vaccine delivery tube, length and diameter, needle length and diameter, needle shape and delay in vaccine consumption after thawing. Elimination or reduction of the adverse effects arising from any one of these noted factors would greatly improve the inoculation process for Marek""s vaccine, specifically, and for live vaccines, generally.
A conventional needle configuration for drawing a vaccine fluid into a syringe and subsequently delivering the vaccine from the syringe to a vaccine delivery system, such as an automated injection system for avian embryos as disclosed in U.S. Pat. No. 4,681,063, is illustrated in FIG. 1. As shown, a conventional syringe needle, generally designated by reference numeral 110, is attached to a conventional syringe, generally designated by reference numeral 112. The syringe 112 has a hollow tubular barrel 114 having a chamber 116 for retaining fluid, such as the live vaccine. The syringe 112 also has a plunger with a flexible plug (not shown). As is common in the art, the plug will sealingly engage against an inner surface 118 of the syringe barrel 114, with the plunger being pulled out of the chamber 116 to draw fluid into the chamber and being pushed into the chamber 116 to inject fluid out of the chamber.
The syringe 112 has a standard tubular extension 120 projecting from end 122 of the barrel 114. The tubular extension 120 has a cylindrical axial passageway 126 which communicates with the syringe chamber 116 and needle assembly 110, when attached. The tubular extension 120 is surrounded by a collar 124 which has internal male threads 125 so that the needle assembly 110 can be sealingly attached in a conventional manner by outwardly extending flange 138 screwing downwardly on threads 125.
The needle assembly 110 includes an injection needle or cannula 133 and a needle retainer 128. The retainer 128 is mounted on the forward end of the syringe 112 as previously described to retain the needle assembly 110 in generally axial alignment with the syringe 112 and tubular extension 120. The needle 133 is made of conventional needle materials, such as stainless steel for strength and chemical compatibility, and the retainer 128 is preferably made of a suitable plastic material which can be easily molded around the end 136 of needle 133.
The needle 133 includes a hollow central passageway or lumen 134 and a sharpened tip 130 at its outer end 132 formed by an angled cut of the hollow needle. The needle 133 is preferably surrounded by a cap or sheath (not shown) before the needle is used for sterility, and the sheath is easily removed in a conventional manner when the needle and syringe are ready for use.
To hold the needle assembly 110 in generally axial alignment with the syringe, the retainer 128 has an axial bore 141 and an outwardly projecting rim or flange 138 at the syringe receiving end. The axial bore 141 is sized to fit in sealing engagement over the tubular extension 120, while the outer circumference of the rim or flange 138 engages the threads 125 on the inner wall of surrounding collar 124. As assembled, the outwardly projecting rim or flange 138 snugly fits down into space 139 between the outer surface 142 of the tubular extension 120 and the inner surface of the collar 124. Thus, mounted on the syringe 112, the hollow central passageway or lumen 134 of the needle portion 133 aligns with the passageway 126 of the tubular extension 120 and the chamber 116 of the syringe 112.
The conventional syringe and needle assembly as previously described and shown in FIG. 1 is commonly used and well known. The assembly is particularly intended for single dosage use, and for storage, transportation, and injection while filled with fluid. It is also the standard assembly for transferring concentrated live virus vaccines, such as Marek""s vaccine, from supply ampules to diluent storage containers or bags where it is appropriately diluted for delivery to a specimen to be vaccinated, such as chicken egg embryos and the like, by known vaccine delivery machines or systems. It has been surprisingly discovered that the use of this conventional syringe and needle assembly for transferring live vaccines creates unexpected problems in the destruction of the live cells caused by turbulence of the vaccine during both the drawing of the vaccine into the syringe chamber 116 and the discharge of the vaccine from the chamber 116, through the passageway 126 of extension 120 and the passageway 134 of the needle 133.
While it was known that turbulence could be detrimental to the live cell count of various vaccines, including Marek""s vaccine, it was not appreciated that the conventional syringe and needle assembly as commonly used for transfer of these vaccines would cause significant turbulence and that this turbulence could significantly reduce the live cell count, or the PFUs of the vaccine, including Marek""s vaccine, both during the filling of the syringe barrel 114 and during injection of the vaccine out of the syringe.
The problem with this commonly used needle and syringe assembly is that a tubular gap, indicated by numeral 140 in FIG. 1, is formed between the top of the tubular extension 120 and the rear part 136 of the needle 110. It has been found that this tubular gap 140 causes turbulence in the fluid flowing between needle 133 and tubular extension 120, both during the filling of the syringe barrel 114 and during the injection of the vaccine from the syringe.
To understand the effect of turbulence in the context of the present invention, it is believed that a brief discussion of flowing fluid would be helpful. When fluid flows slowly and smoothly, the flow is called laminar. At fast velocities, however, the inertia of the fluid overcomes fluid frictional forces and turbulent flow results. When a fluid is flowing this way, it flows in eddies and whorls (vortices), and there is much more drag than when the flow is laminar.
Turbulence is composed of eddies: patches of zigzagging, often swirling fluid, moving randomly around and about the overall direction of motion. Technically, the chaotic state of fluid motion arises when the speed of the fluid exceeds a specific threshold, below which viscous forces damp out the chaotic behavior. As applied to live vaccines, such as Marek""s vaccine, turbulence that disrupts the flow causes the live cells to bounce off one and another. This bouncing during the turbulence kills live cells, thus reducing the PFUs which can be delivered by the vaccine.
Upon studying the conventional syringe and needle assembly, it has also been determined that damage to the live cells of the concentrated vaccine also occurs at the outer end 132 of the needle 133 due to the sharpened tip 130 during the drawing of the vaccine into the syringe barrel 114. The live cells of known vaccines for inoculating chicken and other avian species embryos, including Marek""s vaccine, as well as the live cells in many other live cell fluids are very fragile. Damage to the outer membrane or cell wall can cause rapid destruction of the live cell. It has been found that the sharp edges of the needle tip tend to physically damage the cell wall or membrane of the live cells when drawn into the needle. This damage can be very detrimental to the live cells in known vaccines, particularly Marek""s vaccine, and substantially reduce the PFUs which can be delivered.
In view of the turbulence generated by conventional needle designs and the sharp needle tip, as well as other problems and disadvantages of the prior art, the present invention seeks to provide improved needle designs and needle assemblies which are particularly adapted for transferring concentrated live vaccines and other fluids containing live cells. More specifically, the needle assemblies of the present invention are specifically shaped and adapted to fill the tubular gap between the needle retainer and the syringe to reduce the turbulence and destruction of the live cells of the vaccine, thus delivering higher PFU values. Additionally, the present invention includes a needle design which is utilized during the filling of the syringe to minimize the physical damage to the live cells of vaccines and other fluids caused by the sharp edges at the tip of the needle.
In order to minimize the turbulence and promote a laminar flow of the concentrated vaccine, and to minimize physical damage to the live cells, the needle assemblies of the present invention modify the standard needle structure in two important ways.
First, the needle retainer 128 is modified to include an insert or filler to fill the gap 140 while at the same time providing an axial passageway to connect passageway 126 of the syringe tubular extension 120 with the entrance to the passageway or lumen 134 of the needle 133. The axial passageway of the gap insert or filler is designed to provide a smooth flow transition between the larger diameter extension passageway 126 and the smaller diameter needle passageway 134. The insert or filler is sized so that the end facing the outer surface 145 of the extension 120 sealingly abuts the surface 145 when the needle retainer 128 is screw threaded into collar 124 and the axial bore 141 reaches tight sealing engagement around syringe extension 120. In order that the fluid can have a continuous laminar flow, the gap insert or filler has an inner throughbore which is preferably funnel or conically shaped. The top opening of the throughbore is substantially equal in diameter to the rear opening of the needle lumen, and the rear opening of the throughbore is substantially equal in diameter to the opening of the syringe extension passageway. Thus, the live cells are not bouncing around in the gap 140 and turbulence is minimized.
Second, a different needle tip is used for drawing the concentrated vaccine from the ampule, in particular, a needle tip having a funnel shape to form an open mouth at the entrance end of the needle or cannula 133. With this funnel shape, the needle end can more gently draw the vaccine into the hollow needle passageway 134 without damage to the cell wall caused by the sharp edges of pointed tip 130. Since damage to the cell wall im minimized, the destruction of the live cells is reduced and each dosage of vaccine has higher PFUs to vaccinate the embryos.
A needle with an open mouth in accordance with the present invention can be used when drawing the concentrated vaccine up from the ampule because the ampule has an opening for withdrawing the vaccine therefrom and does not need to be punctured by a sharp needle tip. On the other hand, when delivering the concentrated vaccine to a delivery system, it is typically desirable to puncture the container containing the vaccine diluent, through the injection port, or the container for holding the diluted vaccine for delivery to the avian embryos. In such circumstances, the needle tip must have a sharpened point such as used in the standard needle configuration. However, when delivering the concentrated vaccine from the syringe through the needle portion, the vaccine does not encounter the sharp edges at the needle tip, in contrast to drawing the concentrated vaccine into the needle. Hence, the standard needle tip does not cause significant disadvantages during the delivery of the concentrated vaccine into the diluent bag or other container.
In one embodiment of the present invention the needle retainer is modified with the requisite insert or filler to provide a smooth laminar flow between the needle and the syringe. The needle also has a funnel shape to form an open mouth at its tip. The needle is further modified, however, to have a breakaway tip so that after the concentrated vaccine has been drawn into the syringe through the open mouth, the outer extremity of the needle can be broken away to leave a sharp point needle tip for subsequently injecting the concentrated vaccine into the diluent bag or other container. The breakaway tip is formed by a diagonally-positioned weakened area in the needle near the tip. The weakened area can be molded into the needle, if the needle is made from plastic, or scored or ground into the needle outer surface if the needle is made from metal.
It is therefore an object of the present invention to provide a needle assembly which can be assembled on a conventional syringe and which minimizes the turbulence imparted to a concentrated vaccine, especially a vaccine containing live cells, so as to avoid destruction of the live cells during transfer of the vaccine using the needle and syringe assembly.
Another object of the present invention is to provide a needle assembly in accordance with the preceding object and which includes a needle retainer having a tubular insert or filler with an inner funnel or conical shaped throughbore such that the opening adjacent the rear of the needle has a diameter substantially equal to the needle diameter and the opening adjacent the syringe extension has a diameter substantially equal to the diameter of the extension passageway.
A further object of the present invention is to provide a needle assembly for attachment to a conventional syringe which has a needle tip that serves to reduce the physical damage imparted to the live cells contained in a concentrated vaccine or other fluid during the drawing of the vaccine into the syringe.
A still further object of the present invention is to provide a needle assembly in accordance with the preceding object in which the needle tip has an open mouth with the mouth diameter larger than the diameter of the needle passageway.
Still another object of the present invention is to provide a needle assembly in accordance with the preceding objects which has a needle tip that serves to reduce the physical damage imparted to the live cells contained in a concentrated vaccine or other fluid during the drawing of the vaccine into the syringe and has a breakaway needle configuration which, upon removal of the needle end, leaves a sharpened needle tip of standard configuration.
A final object of the present invention to be set forth herein is to provide needle assemblies which can be installed on a conventional syringe and which will conform to conventional forms of manufacture, be of simple construction and easy to use so as to provide needle assemblies that are economically feasible, highly strong and durable, and relatively trouble-free in use.
These together with other objects and advantages which will become subsequently apparent reside in the details of construction and operation as more fully hereinafter described and claimed, reference being had to the accompanying drawings forming a part hereof, wherein like numerals refer to like parts throughout.